(R)-5-Aminomethyl-pyrrolidin-2-one hydrochloride

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6-Bromo-1-((5-oxopyrrolidin-2-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one. 3,5-Dibromopyrazin-2-amine (253 mg, 1 mmol), 5-(aminomethyl)pyrrolidin-2-one hydrochloride (150 mg, 1 mmol), diisopropylethylamine (0.5 mL), and dimethylsulfoxide (2 mL) were heated in a Biotage Emrys Optimizer microwave reactor at 150° C. for 2 h to afford crude 5-((3-amino-6-bromopyrazin-2-ylamino)methyl)pyrrolidin-2-one. MS (ESI) m/z 286.0 [M]+, 288.0 [M+2] +. 1,1′-Carbonyldiimidazole (243 mg, 1.5 mmol) was added to the reaction mixture and the solution was heated again in a Biotage Emrys Optimizer microwave reactor at 150° C. for 10 min. The product was purified by reverse-phase semi-preparatory HPLC (10-70% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min). The product fractions were concentrated and then triturated with ether to give a white solid. MS (ESI) m/z 312.0 [M]+, 314.0 [M+2]+.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6-Bromo-1-((5-oxopyrrolidin-2-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one. 3,5-Dibromopyrazin-2-amine (253 mg, 1 mmol), 5-(aminomethyl)pyrrolidin-2-one hydrochloride (150 mg, 1 mmol), diisopropylethylamine (0.5 mL), and dimethylsulfoxide (2 mL) were heated in a Biotage Emrys Optimizer microwave reactor at 150° C. for 2 h to afford crude 5-((3-amino-6-bromopyrazin-2-ylamino)methyl)pyrrolidin-2-one. MS (ESI) m/z 286.0 [M]+, 288.0 [M+2]+. 1,1′-Carbonyldiimidazole (243 mg, 1.5 mmol) was added to the reaction mixture and the solution was heated again in a Biotage Emrys Optimizer microwave reactor at 150° C. for 10 min. The product was purified by reverse-phase semi-preparatory HPLC (10-70% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min). The product fractions were concentrated and then triturated with ether to give a white solid. MS (ESI) m/z 312.0 [M]+, 314.0 [M+2]+.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6-Bromo-1-((5-oxopyrrolidin-2-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one. 3,5-Dibromopyrazin-2-amine (253 mg, 1 mmol), 5-(aminomethyl)pyrrolidin-2-one hydrochloride (150 mg, 1 mmol), diisopropylethylamine (0.5 mL), and dimethylsulfoxide (2 mL) were heated in a Biotage Emrys Optimizer microwave reactor at 150° C. for 2 h to afford crude 5-((3-amino-6-bromopyrazin-2-ylamino)methyl)pyrrolidin-2-one. MS (ESI) m/z 286.0 [M]+, 288.0 [M+2]+. 1,1′-Carbonyldiimidazole (243 mg, 1.5 mmol) was added to the reaction mixture and the solution was heated again in a Biotage Emrys Optimizer microwave reactor at 150° C. for 10 min. The product was purified by reverse-phase semi-preparatory HPLC (10-70% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min). The product fractions were concentrated and then triturated with ether to give a white solid. MS (ESI) m/z 312.0 [M]+, 314.0 [M+2]+.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6-Bromo-1-((5-oxopyrrolidin-2-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one. 3,5-Dibromopyrazin-2-amine (253 mg, 1 mmol), 5-(aminomethyl)pyrrolidin-2-one hydrochloride (150 mg, 1 mmol), diisopropylethylamine (0.5 mL), and dimethylsulfoxide (2 mL) were heated in a Biotage Emrys Optimizer microwave reactor at 150° C. for 2 h to afford crude 5-((3-amino-6-bromopyrazin-2-ylamino)methyl)pyrrolidin-2-one. MS (ESI) m/z 286.0 [M]+, 288.0 [M+2] +. 1,1′-Carbonyldiimidazole (243 mg, 1.5 mmol) was added to the reaction mixture and the solution was heated again in a Biotage Emrys Optimizer microwave reactor at 150° C. for 10 min. The product was purified by reverse-phase semi-preparatory HPLC (10-70% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min). The product fractions were concentrated and then triturated with ether to give a white solid. MS (ESI) m/z 312.0 [M]+, 314.0 [M+2]+.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6-Bromo-1-((5-oxopyrrolidin-2-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one. 3,5-Dibromopyrazin-2-amine (253 mg, 1 mmol), 5-(aminomethyl)pyrrolidin-2-one hydrochloride (150 mg, 1 mmol), diisopropylethylamine (0.5 mL), and dimethylsulfoxide (2 mL) were heated in a Biotage Emrys Optimizer microwave reactor at 150° C. for 2 h to afford crude 5-((3-amino-6-bromopyrazin-2-ylamino)methyl)pyrrolidin-2-one. MS (ESI) m/z 286.0 [M]+, 288.0 [M+2] +. 1,1′-Carbonyldiimidazole (243 mg, 1.5 mmol) was added to the reaction mixture and the solution was heated again in a Biotage Emrys Optimizer microwave reactor at 150° C. for 10 min. The product was purified by reverse-phase semi-preparatory HPLC (10-70% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min). The product fractions were concentrated and then triturated with ether to give a white solid. MS (ESI) m/z 312.0 [M]+, 314.0 [M+2]+.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6-Bromo-1-((5-oxopyrrolidin-2-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one. 3,5-Dibromopyrazin-2-amine (253 mg, 1 mmol), 5-(aminomethyl)pyrrolidin-2-one hydrochloride (150 mg, 1 mmol), diisopropylethylamine (0.5 mL), and dimethylsulfoxide (2 mL) were heated in a Biotage Emrys Optimizer microwave reactor at 150° C. for 2 h to afford crude 5-((3-amino-6-bromopyrazin-2-ylamino)methyl)pyrrolidin-2-one. MS (ESI) m/z 286.0 [M]+, 288.0 [M+2]+. 1,1′-Carbonyldiimidazole (243 mg, 1.5 mmol) was added to the reaction mixture and the solution was heated again in a Biotage Emrys Optimizer microwave reactor at 150° C. for 10 min. The product was purified by reverse-phase semi-preparatory HPLC (10-70% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min). The product fractions were concentrated and then triturated with ether to give a white solid. MS (ESI) m/z 312.0 [M]+, 314.0 [M+2]+.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6-Bromo-1-((5-oxopyrrolidin-2-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one. 3,5-Dibromopyrazin-2-amine (253 mg, 1 mmol), 5-(aminomethyl)pyrrolidin-2-one hydrochloride (150 mg, 1 mmol), diisopropylethylamine (0.5 mL), and dimethylsulfoxide (2 mL) were heated in a Biotage Emrys Optimizer microwave reactor at 150° C. for 2 h to afford crude 5-((3-amino-6-bromopyrazin-2-ylamino)methyl)pyrrolidin-2-one. MS (ESI) m/z 286.0 [M]+, 288.0 [M+2] +. 1,1′-Carbonyldiimidazole (243 mg, 1.5 mmol) was added to the reaction mixture and the solution was heated again in a Biotage Emrys Optimizer microwave reactor at 150° C. for 10 min. The product was purified by reverse-phase semi-preparatory HPLC (10-70% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min). The product fractions were concentrated and then triturated with ether to give a white solid. MS (ESI) m/z 312.0 [M]+, 314.0 [M+2]+.